This proposal focuses on the structure and stability of the leucine zipper, a recently discovered sequence motif that mediates dimerization of a large family of eukaryotic transcription factors. The long term objectives of the proposed research are to understand the energetic and structural basis for the stability and specificity of leucine zipper dimerization. The proposed experiments will provide significant insights into protein-protein interactions, protein stability, structure-function relationships in coiled coil proteins, transcriptional regulations, oncogenesis and molecular recognition. The specific aims of the research are: (1) To complete the high resolution crystallographic refinement of the x-ray crystal structure of a synthetic peptide corresponding to the leucine zipper of the yeast transcriptional activator GCN4. (2) To crystallize the leucine zipper sequences of the nuclear oncogene products Fos and Jun. (3) To quantify the stabilizing contributions of individual interactions in the GCN4 leucine zipper using structural and thermodynamic studies of peptide variants.